Resolution of Psoriatic Arthritis Pain in 1 Month

TREATING CLINICIAN: Joe Mather, MD, MPH&TM

Patient Info:

• Carolyn, 72 y/o, Female
• Previous Dx
  • Psoriatic arthritis
  • Atopic dermatitis
• Rx
  • n/a
• Chief Complaints
  • Constipation
  • Skin rash, swelling, redness, burning, oozing, blistering, flaking – 4
  • Joint swelling – 3
  • Fatigue, generally feeling sick – 3
  • Insomnia secondary to terrible itching all night

Visit 1 (Day 1) – History and Exam:

Initial Impression:

• Carolyn is a 72-year-old woman with a positive demeanor, suffering with psoriatic arthritis
• Dx/Rx:
  • Not currently taking any medications
  • Synthroid + Atarax from PCP

• Previous testing from PCP:
  • Jan 2021
    • TSH 8.9, Free T4 0.8
  • March 2021 (a few days before our first appointment)
    • LDL 198, TRI 121, TSH 12.55, 4F 0.9, AST 20/ALT14, A1c 5.4,
• Onset:
  • Constipation as a child, through her 20s.
  • Experienced chronic cracking, peeling, red, itchy fingers in her 20s. Continued until recently. Now it’s a “raging body rash.”
  • Graves Disease: treated with radiation in her 20s.
  • Carolyn was diagnosed with Psoriatic arthritis in 2013. She initially experienced mild symptoms which have steadily worsened to the present. Historically, her flares would come and go every 2-3 months, but since Dec 2020 she has been quite miserable.
    • She saw a Rheumatologist who recommended Humira, Carolyn was resistant to biologic therapy.
  • She did get COVID in Jan 2021, recovered normally.

• Prior Treatments:
  • Magnesium
• DDX:
  • Food sensitivities, GI dysbiosis, mold, metals
• Previous Diets:
  • Gluten-Free
  • Dairy-Free
  • Paleo
  • Low Histamine
  • Did best on paleo “but did not stop the rash cycle”
• Prognosis:
  • Good prognosis considering she has not tried any foundational GI therapies. She has untreated hypothyroidism, and her fatigue is likely to improve on medication. She has felt the best on Paleo which increases the odds of a good response to a stricter dietary regimen.
• Notes / Initial Treatment:
  • I recommended that Carolyn follow up with her PCP before her next visit with me and ask about starting Synthroid given her increasing TSH and fatigue. I also recommended that she ask for a prescription for Atarax to take at night to reduce nighttime itching to improve her sleep.
  • Carolyn had already ordered all 3 probiotics that I asked her to start right away.
  • As Carolyn was suffering and already had seen improvement in the past with a Paleo Diet, I asked her to start right away with the AIP Diet.

Visit 2 (a few days later) – Testing and Initial Recommendations

Testing:

• Tests Ordered
  • Bloodwork: Heavy metals panel, GGT, TSH with reflex T4
  • Doctors Data urinary heavy metals kit
  • Optional:
    • GI-MAP stool test
    • Real Time Labs urine mycotoxin test
• Rationale
  • In my experience, autoimmunity is most commonly generated by three issues: GI dysfunction, mold, and metals. It is very helpful to know what issues are at play for long term management.
  • I recommended that Carolyn start with inexpensive bloodwork and a urine test to screen for heavy metals, as well as a repeat of thyroid hormones to confirm hypothyroid status.
  • Optional GI-MAP indicated given association of pathogens with autoimmunity
  • Optional RTL given the association between mycotoxins and autoimmunity

Recommendations:

• GI: Lacto-bifido probiotic blend, s. boulardii, soil-based probiotic, gut-healing nutrients
  
• Diet: AIP
• Do a 2-4 day trial of the Elemental Diet
• Rationale
  • Given the severity of her symptoms, I recommended that she jump right into AIP and the supplemental program that has helped previous patients with autoimmunity
  • Also recommended she try a short course of Elemental Diet early on, to get an early sense if she will respond to fasting or Elemental Diet so that they can be worked into her plan. (In my experience, these therapies seem to be particularly good for psoriasis.)
• Follow up: 4-5 weeks

Visit 3 – Lab Interpretation and Treatment Evaluation

Subjective Assessment:

• Improved:
  • Rash
  • Fatigue
  • Sleep issues
• Same:
  • Constipation
• Worse:
  • n/a

Lab Interpretation:

• Doctors Data Urine Toxic Metals:
  • Elevated Lead 1.4
• Real Time Labs Urinary Mycotoxins:
  • Ochratoxin A, Aflatoxin – 99th% reference range
  • Trichothecene, Zearalenone – 50th% reference range
  • Gliotoxin – 25th% – reference range

• Professional Co-Op Testing at LabCorp:
  • Blood Lead 3 (90th% 2.14)
  • Thyroid TSH 2.54, F4 0.97, GGT 10
• GI-MAP – still waiting for patient’s sample

Impression:

• “I can say I feel good, and haven’t been able to say that in months! Arthritic pain – I have none! Fatigue – I have energy back.”
• “Rash disappeared everywhere except the forearm and hands. It looks wonderful. The rash around my mouth has receded.”
• Fasting – did well the first time and repeated a second course.
• Itching on arms is reduced, she is sleeping better, using Benadryl at night.
• Thyroid labs now normal after a short time on Armour.

Recommendations:

Starting

• Binding protocol:
  • Activated charcoal
  • Chlorella tablets
  • Bentonite clay
  • Modified citrus pectin
• Rationale
  • I had Carolyn start low-dose binders to begin to address her toxic load from mycotoxins and lead. She has multiple mycotoxins strongly positive, so broad spectrum binders are indicated. MCP is particularly helpful for heavy metal detox.
    • I speculate that binders will help improve systemic inflammation in her case. These substances bind endotoxins, as you’ll learn in the review below. Given her response to the elemental diet, I suspect that she has a large dysbiotic load in her gut, intestinal permeability, and a lot of endotoxins/ LPS.
  • Testing:
    • I’d like you to reach out to some local home inspectors to help you understand if you are being exposed to mold or lead in your current home.
  • Follow up: 4-5 weeks

Clinician’s Comments

Clinical Rule: Gut before mold/metals.

• Although Carolyn has a large toxic load, we did not need to immediately address those things to make a very significant shift in her symptoms. In fact, had we jumped right to metals, mold, and tick-borne illness we likely would have missed the opportunity to get a quick resolution of her autoimmunity and inflammation.
• Treating the gut first will enhance her ability to detoxify the mold and metals.

A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins

PMID: 23710148

Study Purpose

• Janette Hope has written a masterful and extremely helpful review. This comprehensive review of mold toxicity, published in 2013, should be required reading for any physician treating mold related illness.
• I’ve presented the main sections of her paper with her words in italics, and my comments below in bullets.

Introduction

Symptoms and illness due to exposure result from varying mechanisms including infection, toxicity, allergy, irritant effects, and systemic inflammation. Additionally, individual responses to exposure vary based on genetic makeup, duration and severity of exposure, and underlying health and nutritional status. While it is often difficult to determine the contribution of the many components of water-damaged buildings, studies on illness from exposure to damp/water-damaged environments have been consistent in identifying the overall exposure itself as being the main factor associated with adverse health effects [4, 5]. Individual components of exposure that have been identified include: mold and mold spores, mycotoxins, bacteria, bacterial endotoxins and other cell wall components, protozoa (amoeba), increased presence of rodents, insects and dust mites, and increased deterioration of building materials with consequent offgassing of toxic fumes such as formaldehyde [4, 5].

• Although much attention is paid to the mold toxins, illness due to mold is from many causes. I increasingly think of mycotoxins as a proxy for the larger “hidden” toxic load (endotoxins, VOCs, mold fragments, allergens….)

Molds and Mycotoxins

Thousands of mycotoxins have been identified to date; however, we will limit discussion to those currently felt to have the most relevance to health effects resulting from water-damaged indoor environments.

• Each of the main groups of toxins Aflatoxins, Ochratoxins and Trichothecenes are produced by a variety of different mold species. Dr. Hope reviews the literature of the various harmful effects of these toxins in some detail. Main points:

Aflatoxin B1 (AFB1) is genotoxic, immunotoxic, hepatotoxic, mutagenic, and considered one of the most abundant, most toxic, and most potent naturally occurring carcinogenic substances known and is the leading cause of liver cancer in many developing countries [27–29].

Ochratoxin A is produced by Aspergillus ochraceus, Aspergillus niger, Aspergillus, and species of Penicillium, Petromyces, and Neopetromyces. OTA is a nephrotoxic, genotoxic, immunotoxic, and [30] neurotoxic [22, 31] mycotoxin which is a known carcinogen in animals and a class 2B, possible human carcinogen.

Trichothecenes are produced by Stachybotrys, Fusarium, and Myrothecium mold and include T2 toxin, deoxynivalenol (DON), and the macrocyclic trichothecenes satratoxin, and verrucarin [36].

• I suspect that future research will prove a causal relationship between mold toxins and more types of cancer and chronic disease.

Bacteria and Endotoxins

• In this section, Dr. Hope reviews research showing elevated levels of certain bacteria in water-damaged homes. She mentions gram-positive Actinobacter, Streptomyces, Mycobacteria, and Nocardia which are associated with pulmonary diseases, as well as gram-negative Pseudomonas, a producer of endotoxins such as LPS. These components of bacterial cell walls produce an extremely strong inflammatory response.

Furthermore, studies have shown that endotoxins act synergistically with mycotoxins to enhance the cytokine-mediated inflammatory response [24, 44].

In one study, LPS was injected intracerebrally into a neonatal rat to trigger brain inflammation and it was found that the application of the pesticide rotenone resulted in motor and neurobehavioral impairments in the rats exposed to LPS and not in the unexposed rats [50].

• In these animal studies, it was the combination of endotoxin and mycotoxin that generated the most harmful effects. This explains the benefit of first treating the gut in our mycotoxic patients, as reducing bacterial dysbiosis and intestinal permeability will reduce the total endotoxic load.

Microbial Volatile Organic Compounds (MVOCs) and Other Sources of VOCs

MVOCs are found in water-damaged homes. However, their role as a marker for mold contamination and as a significant cause of human illness is still being elucidated. Mold VOCs have remained difficult to measure.

Routes of Exposure

While foodborne exposure to mycotoxins and fungal contaminants has been well researched, substantial information about airborne and transdermal routes of exposure also exists. Airborne exposure is likely the most significant route of exposure in water-damaged indoor environments; however, transdermal and potentially foodborne exposure through contact with indoor mycotoxins can also occur in these settings.

• There is controversy regarding the importance of different routes of exposure. It is my observation that the respiratory and dermal routes are much more clinically relevant than foodborne exposure. My patients with mold toxicity will be very immediately made sick upon entry of a mold-contaminated building but seem to suffer no setback when consuming higher levels of “moldy food” coffee, grains, corn (for those that can tolerate these foods).
  • I suspect that gastric acid and immune defense including mast cells are able to eliminate or neutralize most mold toxins that enter orally, while toxins that are inhaled or absorbed into the skin bypass this defense.

Toxicity from inhaled mycotoxins appears to be very significant. In a study involving rats and guinea pigs, toxicity from inhaled T2 mycotoxin was 20 times as toxic as intraperitoneally administered toxin in rats and at least twice as toxic in guinea pigs [56]. Clinical symptoms seen in these animals immediately after exposure were tremors, lethargy, stilted gait, and in some cases prostration.

• Tremors, lethargy, exhaustion, brain fog, and chronic fatigue are also extremely common in other mammals exposed to mold…!

Intact spores are not the only source of aerosolized exposure. It has been shown that fungal fragments, often submicron-sized, can be released at 320 times higher level than spores and that the number of released fragments cannot be predicted based on the number of spores [62]. Increased reactivity of smaller fragments has been documented as they have the potential to penetrate deeper into the respiratory tract than intact spores which are generally greater than 2.5 microns [38, 62].

• Fungal fragments may be released at hundreds of times higher levels than spores and as they are smaller than spores may be more readily absorbed through the pulmonary tissues and skin.

One study showed that aflatoxin B1, OTA, citrinin, T2 toxin, zearalenone all penetrated human skin in vitro and that ochratoxin had the highest permeability [65].

• This is why remediation workers wear hazmat suits. Please don’t let your patients stay in their homes while their home is being remediated.

Mechanisms of Illness

Illness resulting from exposure to water-damaged buildings can be caused by infection, toxicity, allergy, and inflammatory responses triggered by exposure to one or more of the agents present in water-damaged buildings and are often mediated by oxidative stress. Types of disorders that can be seen resulting from water-damaged environments, mold, mycotoxins, and bacteria include, infections and mycoses, chronic and fungal rhinosinusitis, IgE-mediated sensitivity and asthma, other hypersensitivity reactions, pulmonary inflammatory disease, immune suppression and modulation, autoimmune disorders, mitochondrial toxicity, carcinogenicity, renal toxicity, neurotoxicity, and DNA adducts to nuclear and mitochondrial DNA causing mutations [39].

• It is because of the wide-ranging and devastating consequences of mold that I encourage my patients to stay on binders until the mycotoxin load is completely cleared.
• Not all patients have a toxic response to mold, some will have an allergic response.

Most commonly, however, many mechanisms are interacting in an individual at any given time, making it imperative to address the illness with a comprehensive, multifaceted approach. Although respiratory symptoms are common from exposure to water-damaged indoor environments, it is important to note that a typical patient presents with multiple symptoms which are often debilitating, including fatigue, neurocognitive symptoms, myalgia, arthralgia, headache, insomnia, dizziness, anxiety, depression, irritability, gastrointestinal problems, tremors, balance disturbance, palpitations, vasculitis, angioedema, and autonomic nervous system dysfunction [76, 77]. The development of new onset chemical sensitivity is also commonly seen after exposure and can have a severe impact on a person’s life [77].

• Conditions that strongly predict that mold is causing your patient’s illness include:
  • New onset asthma in an adult
  • New onset chemical sensitivity
  • A diagnosis of POTS

Clearly, genetic individuality plays a role in response to exposure and response to treatment in ways that are still being elucidated.

• It is common for one or two members of a family of four to become ill as a result of mold exposure while the other two members of the family remain healthy.

➕ Neurocognitive Symptoms

Some of the most distressing symptoms encountered by patients following exposure to water-damaged indoor environments and toxigenic molds include neurocognitive disturbances.

• The brain fog, memory loss, and poor executive function is distinctive and palpable in this illness.

A disturbing study, conducted in Poland, measured IQ scores in children exposed to indoor mold for greater than two years, showed statistically significant IQ deficits in children exposed to indoor mold [79]. This study controlled for multiple variables and involved testing of 277 term babies at age 6 years using the WISC-R scale of intelligence and tests of neuropsychological function. Children exposed to indoor molds showed a statistically significant deficit of approximately 10 points. Additionally, it was shown in this study that longer exposure to indoor molds tripled the risk for low IQ scores defined as values below the 25th percentile.

• Mold reduces IQ

Patients who have developed symptoms as a result of exposure to mold and mycotoxins can present similarly with several classic neurologic disorders including pain syndromes, movement disorders, delirium, dementia, and disorders of balance and coordination [87].

• Mold directly poisons the central nervous system. It is not uncommon to see patients develop tinnitus as a result of mold exposure. I have seen two cases resolve or improve via avoidance and binders.
  • I suspect that the eighth Cranial nerve (vestibulocochlear nerve) is being directly damaged in many patients. Inflammation in its two branches, auditory and vestibular, would explain the high occurrence of tinnitus as well as balance and coordination problems or POTS. I also suspect a large number of cases of Meniere’s Disease are being caused by mold exposure.

➕ Oxidative Stress

Oxidative stress is being increasingly understood as a significant mechanism of illness from exposure to water-damaged buildings. For example, ochratoxin A, which is commonly found at elevated levels in persons exposed to water-damaged homes, is a known cause of cellular changes associated with oxidative stress. A recent study of human blood mononuclear cells exposed to OTA showed increased levels of reactive oxygen species and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress [21]. Additionally, in this study, OTA-induced DNA strand breaks, G1 phase arrest, and apoptosis of human mononuclear cells, contributing to the immunotoxicity of OTA. Of significance in this study, application of N-acetyl cysteine, a significant glutathione precursor, was able to significantly block some of the negative effects of OTA on the human cells studied.

• There is in vitro and theoretical support for the use of NAC or glutathione in the treatment of mold toxicity.
• Many patients are unable to tolerate glutathione, especially early in treatment when they are still being actively exposed, their toxin load is high and their limbic systems are “on fire.” Later, I consider it a sign of progress if they are able to tolerate glutathione, which I think is generally helpful.
  • When I first began treating mycotoxicity, I had my patients do glutathione provoked urinary mycotoxin tests, using 450 mg of liposomal glutathione. I stopped after finding that around 40% of my patients reacted very poorly to glutathione, often worsening their symptoms for several days, while only 30% seemed to benefit (and 30% didn’t notice any effect).
  • I currently have patients provoke their test with sweating the night before specimen collection with either a hot bath, sauna or exercise. I also have them fast for 12-18 hours as tolerated. I have noticed no decrease in sensitivity comparing glutathione provocation to this approach.

➕ Allergy, Autoimmune Responses, and Non-Allergic Respiratory Disease

Respiratory illnesses have consistently been found to be associated with exposure to water-damaged, damp indoor environments [4, 6, 90]. Examples of this include chronic rhinosinusitis, allergic rhinitis including allergic fungal rhinitis, and sinusitis, asthma (new onset and exacerbations), conjunctivitis, invasive, and allergic pulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and sarcoidosis [9, 90–94].

It has been estimated that 21% of asthma in the United States is attributable to dampness and mold exposure [7],

It is important to note that studies have found that allergic response to mold is often not IgE mediated…Similar results were seen in a Mayo clinic study where a high prevalence of nasal fungal growth was found in both symptomatic rhinosinusitis patients and controls [97] with the most significant difference being the development of eosinophilic mucin and not type 1 hypersensitivity since IgE positivity was not seen in the majority of patients [97].

• Many patients have consulted with an allergist who performs IgE testing. It is helpful to know that negative IgE testing does not rule out mold.
• There is some controversy regarding nasal colonization, and studies are mixed.
  • I find that many patients, especially those who suffer from chronic sinus infections, rhinitis, congestion benefit from intranasal treatment. In my practice, I most commonly use colloidal silver, a xylitol and saline spray, and compounded amphotericin B.

After sensitization, avoiding exposure to allergenic triggers and decreasing the immune response to unavoidable exposures are the main principles of treatment. Allergy to mold clearly places an individual in a damp and moldy indoor environment at increased risk for illness. Allergy testing to mold varies by individual examiner and ranges from comprehensive to minimal panels. Allergy to dust mites can also place an individual in a damp indoor environment at increased risk as dust mites have been shown to grow at amplified levels in damp environments [4]. While avoidance of exposure is always essential, allergy treatment techniques have been used with good success including injection and sublingual immunotherapy [3]. While not all illness resulting from exposure to water-damaged indoor environments is due to mold, some disease clearly is.

• Both injection and sublingual immunotherapies are helpful for patients suffering from mold allergy.

➕ Infection and Colonization

Fungal infections can occur throughout the body and can be a result of exposure to water-damaged indoor environments. These have traditionally been felt to be associated with immunosuppression but have also been seen in immunocompetent hosts [98, 99].

• Mold is often dismissed out of hand by those who are of the opinion that only immunocompromised patients can be made sick from mold. This opinion is not true.

Gut microflora play an essential role in the immune system and detoxification of xenobiotics [108, 109]. Alterations in the gut flora are increasingly being seen to contribute to illness including allergic and autoimmune diseases such as asthma, eczema, and rheumatoid arthritis [108, 109]. Exposure to water-damaged environments, mold, and mycotoxins can result in injury to the gastrointestinal tract [22, 37] and, again, treatments often used to treat illness, such as antibiotics and steroids, can result in profound alteration in gastrointestinal flora, thus decreasing metabolism of mycotoxins and other toxins. Identifying and treating these abnormalities can be significant in restoring health. The use of both bacterial and yeast probiotics, treating infections, and identifying and avoiding food allergens can be significant steps in treatment [110–112].

• It is likely that dysbiosis and a weakened microbiome sets the stage for GI colonization and may predispose some patients to a more toxic or severe case.
• It is my opinion that “pre-treating” the gut is a critical component of a detoxification program. I have seen faster recoveries since I began aggressively treating the gut prior to starting binders or other therapies.

The results of clinical studies of the use of topical (ed: intranasal) antifungals have been mixed. A study of 51 patients with chronic rhinosinusitis who were treated with intranasal amphotericin B found improvement in nasal obstruction and discharge in 75% of the patients and 25% reported complete resolution of symptoms after treatment with improvement starting after one to three months. The only reported side effect was burning on application in 20% of the patients although no patients discontinued therapy due to side effects [100].

• This was an open-label trial of 51 randomly selected patients with chronic rhinosinusitis.

A placebo-controlled double-blind trial of intranasal amphotericin B showed symptoms improved with treatment; however, it did not differ from symptom improvement seen with saline irrigation alone [101].

• The placebo arm in this study may have been active, as the saline itself may have simply physically removed some mold colonization.

Another randomized placebo-controlled, double-blind trial found that intranasal amphotericin B reduced nasal inflammatory mucosal thickening on computed tomography (CT) and endoscopy and reduced intranasal markers for eosinophilic inflammation in patients with chronic rhinosinusitis [102].

• In this study 24/30 patients completed 6 months of therapy.

A Cochrane review concluded there was no benefit to topical or systemic antifungals* for chronic rhinosinusitis [103] which is consistent with a more recent meta-analysis [104].

• Intranasal treatment of mold illness should not be dismissed out of hand based on this review which specifically looks at the chronic rhinosinusitis.
  • All cases of chronic rhinosinusitis are not caused by mold colonization. As seen above, mold can cause pathology via allergic and inflammatory routes. Antifungal treatment would not benefit these cases.
  • Of the 6 studies reviewed, 3 showed benefit, which is different from saying there was no benefit.
  • There may be a therapeutic benefit to saline irrigation used as a control, which masks relative benefit of intranasal antifungal treatment
• * Dr. Hope mentions systemic antifungals here although these reviews specifically only cover the use of amphotericin B intranasal spray in the setting of chronic rhinosinusitis.
• Not all patients exposed to mold need antifungal therapy, some respond perfectly well to avoidance, binders.

Treatment Modalities

➕ Avoidance and Total Load Reduction

The most important component of treatment is avoidance of further exposure to water-damaged environments and items contaminated by those environments as ongoing exposure will thwart any efforts at detoxification and perpetuate a reactive state.

• Patients who are critically ill from mold will not heal if they are being exposed to mold.

Research has shown that none of the commonly used methods for cleaning water-damaged materials such as bleach, ammonia, ultraviolet (UV) light, heating, and ozone were found to completely remove mold and mycotoxins from water-damaged building materials [113]. For this reason, it is safest for patients who have become ill after exposure to water-damaged environments to avoid exposure to items that were present in the contaminated environment.

• I recently had the experience of being re-exposed to mold through contaminated items that I thought were safe, causing a return of symptoms I thought were completely resolved.
• Soft fabric items (couches, pillows), paper, and other porous materials are most problematic compared to hard plastic items that can be wiped clean.

Air spore counts are frequently done and, unfortunately, have significant limitations as they typically collect over a short (5-minute) period and can easily result in false-negative results. The presence of elevation on spore count testing can have significance, however, both in terms of total spore count and types of mold present. The author of one study of schools concluded that a building must be considered unhealthy at spore counts over 1000 spores/m3 [114].

• Helpful information when helping patients interpret the advice from conventional mold testing companies.
• Mold releases spores periodically, which then settle to the floor. Air trapping is often looking for spores exactly where they aren’t located.

A study of a water-damaged hospital highlights limitations of traditional limited testing. The researchers measured multiple markers including culturable fungi and bacteria, endotoxin, submicron-size particles, and markers of fungi (extracellular polysaccharides specific for Penicillium and Aspergillus, ergosterol, and beta-1–3 glucans) and found the presence of submicron-sized particles and markers of microbiological agents was positively associated with a building with historic water-damage and higher prevalence of reported occupant symptoms [115]. The authors proposed that marker compounds in air and floor dust samples may be better indicators of health risk than culturable fungi or bacteria in air or settled dust.

• I feel that ERMI dust testing is more helpful at identifying problematic buildings than dust testing. It is also available directly to patients at a fraction of the cost of air sampling.

While abnormal test results can confirm the presence of a significant problem, they cannot be relied upon to ensure an environment is safe for rehabilitation… It is important to note that an individual who had become ill in a water-damaged environment will likely be most sensitized to that specific environment and items present in the environment and may never be able to return to that environment or be exposed to items from that environment without getting ill. The ability of persons to return to a building without developing symptoms remains the most relevant indicator that a building has been properly remediated [116].

• Mold is so directly toxic to us that exposure can immediately upregulate our immune defenses, and the resulting inflammatory response drives symptoms. The overactivation of the limbic system is very closely tied to this protective response and is likely the reason that mold patients respond so well to limbic retraining.

Unfortunately, common building remediation techniques have not been found to be successful in removing mold and mycotoxins from contaminated materials [113]. In this study, pine and gypsum were deliberately contaminated with Stachybotrys chartarum and Aspergillus versicolor and treated with either peroxide, hot air, flaming, two types of boron-based chemicals, drying, steam, UV light, ammonium chloride, or sodium-hypochlorite-based chemicals. No remediation treatment eliminated all the mycotoxins from the building materials. The study showed that none of the 10 different mold remediation agents and methods tested was able to totally remove mold from the infected materials and that they were ineffective in destroying mycotoxins. The authors conclude that there is a risk of inhaling mycotoxins in buildings even after mold remediation. Although not completely successful, boron, and ammonium-chloride-based chemicals were the most successful in reducing mold and mycotoxin levels.

• As Dr. Jill Crista writes in her book: “Don’t spray and pray.”

A common misperception is that killing mold, which is a relatively easy task, eliminates risk from contaminated environments or items. Unfortunately, this does little to decrease the risk as nonviable fungal spores, fragments, and mycotoxins remain present and, due to their structure, such as with an epoxide ring, [117] they can be extremely difficult to destroy.

• This is the reason that UV light in HVAC systems are not sufficient to remediate sick buildings.

As previously noted, mycotoxins can travel not just on spores, but on fungal fragments which can often be submicron-size [39, 62], allowing inhalation deep into lung tissue and preventing complete protection from occurring with the use of a protective mask.

➕ Total Toxic Load Reduction

In addition to avoidance of further exposure to contaminated items, it is recommended to decrease exposure to other chemical xenobiotic agents including pesticides, heavy metals, volatile organic compounds and fragrances, vinyl chloride, plastics, perfluorinated (nonstick cookware), and other toxins in an effort to reduce total load and improve the ability to detoxify from the exposure to a water-damaged environment. It is common for patients exposed to water-damaged indoor environments to become sensitive to and avoid many chemicals which frequently become noticeable after leaving the environment.

• I am increasingly considering reducing the total toxic load as a strategy to help my patients more quickly reduce their mycotoxic and fungal burden. One reason why some patients are made severely ill and others are not is a higher pre-existing toxic burden which competes with mycotoxins for biotransformation and elimination.

➕ Glutathione

Given the role of oxidative stress in illness from exposure to mold and mycotoxins, the use of glutathione and glutathione precursors plays a large part in treatment.

• For those interested in diving deeper on this treatment, Dr. Hope spends many paragraphs on the theoretical and mechanistic benefits of glutathione
• I do not consider glutathione to be critical as I have now seen many patients recover or improve without its use, but I do feel that it can hasten recovery and improve cognitive function in those who can tolerate it.

It is best to use GSH in conjunction with sequestering agents as administration of GSH appears to allow the mobilization of toxins, including mycotoxins as evidenced in a case of a woman with documented presence of mycotoxins who developed a reversible choreiform movement disorder after she discontinued sequestering agents and was using GSH for six weeks at high dose without sequestering agents [159]. Of note, in this case, was that levels of urinary mycotoxins increased dramatically during the time she was taking GSH without sequestering agents compared to when she was using both GSH and sequestering agents.

• Binders directly lower urinary levels of mycotoxins through fecal excretion (See Sequestering Agents below).
  • Have your patients hold binders for 3 days prior to urinary mycotoxin testing. (Some patients quickly feel worse off binders due to this transient rise of mycotoxins, so be on the lookout for this.)

➕ Sequestering Agents

Sequestering agents refer to nonabsorbable materials capable of binding toxins in the gastrointestinal tract, thus reducing enterohepatic recirculation and ultimately the body burden of toxins. These agents are not absorbed into systemic circulation; therefore, side effects are typically limited to gastrointestinal symptoms and potential malabsorption of medications and nutrients, especially if the dose is poorly timed. Sequestering agents have a large surface area to volume ratio, giving large absorptive capacity.

• It is my clinical experience that sequestering agents can easily cause side effects at too high a dose. The side effect often mimics the original clinical presentation or presents as generalized fatigue or achiness.
  • Mycotoxins are not drawn into the binder as in a sponge, they are very loosely bound to the outside surface of the material and can fall off and be mobilized into the body. Therefore, if too high a dose is given, mycotoxins can be mobilized and drive an inflammatory response.

Several agents have shown specific efficacy in lowering mycotoxin and endotoxin levels including cholestyramine, activated carbons, and chlorella. Additionally, these agents are nonspecific and can bind additional toxins, helping to lower the total body burden of toxins. Of course, they have the potential to bind medications, vitamins, and nutrients and should be taken several hours apart from medications and vitamins and ideally on an empty stomach.

• I have not observed any adverse effects of long-term binders on nutrient, vitamin, or medication levels. I always have my patients take them away from other supplements or medicines.
• Practitioners commonly recommend that patients take binders away from meals, but a variety of animal studies (cows, chicken) have shown improvements in markers of toxicity when simply adding the binders to feeds.
• The fact that the agents are non-specific and have the potential to bind and remove a variety of toxins means that some patients may be improving as the total toxic load is reduced.

A review of the literature shows a successful use of a variety of sequestering agents.

• The remainder of this section reviews the literature supporting the use of a variety of binders, including:
  • Activated Charcoal
  • Sodium Bentonite Clay
  • Chlorella/Chlorophyllin
  • Cholestyramine

Clinicians typically treat with a combination of sequestering agents taken together 2 to 4 times a day, apart from medications and supplements [2].

• I see success dosing my patients with all binders taken together once a day. I feel that the gain in long-term compliance makes this strategy better than multiple doses a day.

➕ Antioxidants and Nutritional Agents

In addition to glutathione, additional antioxidants and vitamins can be helpful. Patients seen in practice have often been ill for a prolonged period of time and need identifying and correcting of nutritional deficiencies essential for optimal detoxification and recovery. Common deficiencies encountered include vitamin D, magnesium, zinc, coenzyme Q10, and B vitamin deficiencies all, of which can adversely affect multiple pathways in the body necessary for detoxification, thereby perpetuating the effects of the toxin exposure.

• In an effort to simplify protocols I do not emphasize additional antioxidants and vitamins for the vast majority of my mycotoxic patients.

➕ Probiotics and Dietary Interventions

Probiotics and various dietary interventions have been studied for their effects on modulating effects of toxins including mycotoxins. These treatments have the potential to have significant beneficial effects as much of the metabolism of toxins occurs via intestinal biotransformation.

The ability of Lactobacillus plantarum and Lactobacillus rhamnosus GAF01 to degrade or bind aflatoxin M1 in vitro was studied in mice [111]. They found both agents were able to remove aflatoxin M1 with superior removal being seen by Lactobacillus rhamnosus. Removal appeared to be by simple binding and the bacteria/aflatoxin M1 complex was stable and only a very small proportion of the mycotoxin was released back in solution

• Probiotics improve mold-related illness through a variety of means. I have seen improved outcomes as I more aggressively treat with probiotics before starting sequestering agents.

➕  Sauna, Exercise, Weight Reduction

A study of 28 persons exposed to mold and mycotoxins included treatment with exercise, physical therapy, and sauna as well as well as IV antioxidants, oxygen therapy, and immunotherapy found improvement in all patients with 27 of the 28 returning to work [3].

• There was likely selection bias in this study, but the bottom line is still impressive.

Dr. Stephen Genuis has studied the excretion of a number of agents in his blood, urine, and sweat (BUS) studies and has found that a number of toxins are found in sweat, with some appearing to be preferentially excreted in sweat [211]. He has identified bisphenol A (BPA) in sweat, even, in some instances when it was not identified in blood or urine, supporting the use of sauna as a possible means to induce excretion of BPA. The presence of phthalates and their metabolites have also been identified in sweat [212] as have heavy metals [213]. Ochratoxin has been found in human sweat [17]. Controlled studies to evaluate for the presence of mycotoxins in sweat would be useful. However, regardless of whether mycotoxins are found, induced sweating will likely reduce the total overall body burden of toxins and support recovery in persons made ill from exposure to water-damaged buildings

• Sauna is excellent for those patients that can tolerate it, as it will mobilize mycotoxins. Too much may cause a patient to crash if they are not ready.

Exercise, whether or not sweating is induced, can have numerous physiologic benefits and should be encouraged at whatever level is tolerated. At least in rats, exercise is shown to prevent oxidative stress and memory deficits with chronic cerebral hypoperfusion [214] and also reduces oxidative stress in hyperphenylalaninemic rats [215]. There are numerous benefits to exercise, and it should be initiated at whatever level is tolerated and gradually increased. Deconditioning, often severe, is frequently seen in those suffering from chronic illness, including illness resulting from exposure to The Scientific World Journal 13 water-damaged buildings. A gradual, escalating approach to resuming exercise can be of great benefit in reversing this.

• An excellent reminder of the importance of exercise.

Conclusion

The treatment of patients who have become ill as a result of exposure to water-damaged buildings involves a comprehensive treatment approach utilizing available nutritional and detoxification strategies. Complete removal from exposure and contaminated items cannot be emphasized enough although it is often not sufficient for some people to regain health. Persistence of symptoms after exposure does occur, unfortunately, and is most likely related to genetic and nutritional factors as well as the severity, duration of exposure, and persistent exposure through cross-contamination. The treatment approaches include the use of sequestering agents, antioxidant support, systemic, nebulized, and intranasal glutathione, probiotics, nutritional support, and the correction of persistent fungal infections or symptomatic colonization. Also, the use of sauna and exercise can be invaluable in helping to restore the health of those injured from their exposure.

Rapid-Fire Research: Ultra-Concise Summaries of Noteworthy Studies

Omega-3 Fatty Acids and Atrial Fibrillation

JAMA. March 2021

• Patients are often counseled to take high dose fish oil to improve cardiovascular health. This editorial reviews recent studies of high dose fish oil in light of an increased risk of atrial fibrillation (AF).
  • “Considered together, the data from the 4 trials suggest, but do not prove, that there may be a dose-related risk of AF with omega-3 fatty acid intake. At a dose of 4.0 g/d, there was a highly statistically significant increase in risk (nearly a doubling).” With an intermediate dose of 1.8 g/d, the increase in risk (hazard ratio, 1.84) did not achieve statistical significance, and with a standard daily dose of 840 mg/d, there was no apparent increase in risk (although the data were consistent with as much as a 24% increase in risk).”
• Patients taking high doses of fish oil should be informed of the risk of AF.

Insufficient Sleep Undermines Dietary Efforts to Reduce Adiposity

PMID: 20921542

• 10 overweight non-smoking adults were randomized into 14 days of moderate caloric restriction with either 8.5 or 5.5 hours of nighttime sleep opportunity.
  • “Sleep curtailment decreased the proportion of weight lost as fat by 55% (1.4 vs. 0.6 kg with 8.5 vs. 5.5 hours of sleep opportunity, respectively; P = 0.043) and increased the loss of fat-free body mass by 60% (1.5 vs. 2.4 kg; P = 0.002). This was accompanied by markers of enhanced neuroendocrine adaptation to caloric restriction, increased hunger, and a shift in relative substrate utilization toward oxidation of less fat.”
• Fat loss was reduced by 55% in the short sleep group.
• The sleep deprived group had increased muscle loss:
  • “Together, these results suggest that the loss of sleep at times of limited food intake amplifies the pattern of ghrelin-associated changes in human hunger, glucose and fat utilization, and energy metabolism. Thus, the increased loss of fat-free body mass during the short-sleep condition of our study may be due to increased conversion of body protein into glucose to support the more prolonged metabolic needs of the waking brain and other glucose-dependent tissues.”

Sleep duration affects risk for ulcerative colitis: A prospective cohort study

PMID: 24780288

• “Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn’s disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined.”
• “Results: Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC.”
• In this large cohort of women, alterations in sleep duration increase the chance of Ulcerative Colitis, but not Crohn’s disease.

Extended Release Lovastatin Does not improve spontaneous bowel movements in patients with IBS-C – Phase 2b study results

Synthetic Biologics Press Release

• A theory emerged that a particular extended release form of lovastatin (SYN-010) would inhibit methane production in patients with IBS-C thereby relieving constipation. The study was cancelled when researchers determined that they were not going to reach their primary endpoint.
• Unfortunately, we won’t have another tool for methane dominant constipation.
  • SYN-010 is a proprietary, modified-release formulation of lovastatin lactone that is intended to reduce methane production by certain microorganisms (M. smithii) in the gut while minimizing disruption to the microbiome to treat an underlying cause of IBS-C. SYN-010 is intended to act primarily in the intestinal lumen while avoiding systemic absorption, thereby targeting a major cause of IBS-C, not just the symptoms.
  • “The Phase 2b study was … designed to evaluate two dose strengths of oral SYN-010 (21 mg and 42 mg) in patients diagnosed with irritable bowel syndrome with constipation (IBS-C). The primary objective of the study was intended to determine the efficacy of SYN-010, measured as an improvement from baseline in the weekly average number of complete spontaneous bowel movements (“CSBMs”) during the 12-week treatment period for SYN-010 21 mg and 42 mg daily doses relative to placebo.”

Practitioner Tip

“Think That You Might Be Wrong”

We should always strive to examine our biases. Our brains are hardwired to produce biases, but simply being aware of their presence helps us from falling into the trap. Here is one of the more common biases from wikipedia:

Confirmation bias is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one’s prior beliefs or values. Flawed decisions due to confirmation bias have been found in political, organizational, financial and scientific contexts. These biases contribute to overconfidence in personal beliefs and can maintain or strengthen beliefs in the face of contrary evidence. For example, confirmation bias produces systematic errors in scientific research based on inductive reasoning (the gradual accumulation of supportive evidence). Similarly, a police detective may identify a suspect early in an investigation, but then may only seek confirming rather than disconfirming evidence. A medical practitioner may prematurely focus on a particular disorder early in a diagnostic session, and then seek only confirming evidence.

Bottom line: Combat confirmation bias by actively looking for information that would disprove your theory.